The central aim of this core is to provide optical imaging services for the pulmonary airways and the lung. These studies will rely on a variety of cutting edge microscopic methods to support other physiologic and molecular approaches to study airway dysfunction in CF, injury and potentially therapy to the airway. Therefore a central imaging core is defined as an integral component of this proposal. The Core will be housed in the Center for Biologic Imaging (CBI) of the University of Pittsburgh Medical Center. This Center is equipped to perform a continuum of optical methods including all types of microscopy essential to this Program Project. Within the scope of this Program light microscopic techniques include conventional histological, immuno-histological, laser confocal, and in situ hybridization methods, as well as multiparametric ratiometric methods and live cell and tissue imaging technologies. Our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate subtle qualitative changes, and this a major function of the Core in this Program. At the electron microscopic level thin section electron microscopy and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses will be employed when needed. A second facet of core function is in the development of novel optical imaging methods specifically for this program. This aspect of core function is described in detail in the preliminary data section. The CBI already has extensive established interactions with the project leaders. We expect these interactions to continue to expand within the formal rubric of this program.